血管周细胞和内皮细胞Cross-talk调控腹膜通透性增高的机制研究

腹膜通透性增高是导致腹透患者不良预后的关键因素。长期腹透患者发生腹膜通透性增高的确切机制仍不明了，是否与腹膜血管周细胞和内皮细胞的Cross-talk发生异常有关？目前国内外未见有关研究报道。为此，本研究拟开展前瞻性的临床研究随访腹透患者的腹膜功能，寻找腹膜通透性增高的早期预测因素；采用体外培养的腹膜微血管内皮细胞，研究炎症、非生理性腹透液和尿毒症血清对细胞表达内皮紧密连接蛋白和通透性的影响，以及血管周细胞和内皮细胞Cross-talk对其的作用；利用尿毒症腹透动物模型探讨血管周细胞和内皮细胞Cross-talk与其腹膜血管周细胞形态分布和覆盖率、微血管渗漏性及腹膜通透性之间的关系，并进一步研究干扰周细胞和内皮细胞间Cross-talk对腹膜形态、微血管渗漏及腹膜通透性的影响，以期阐述长期腹透后腹膜通透性增高的分子调控机制，为今后尿毒症腹透患者防治腹膜功能衰竭提供新的理论依据。

High peritoneal permeability develops with the duration of continuous peritoneal dialysis (PD), leading to deterioration of peritoneal function and ultimately, ultrafiltration failure (UFF), which accounts for the major cause of dropout of long-term PD therapy. However, the mechanisms of increased peritoneal permeability remain unclear. The present study: 1. Stable PD patients are enrolled and prospectively followed up to screen the early predictors for development of high peritoneal permeability; 2. Primary human omental tissue endothelial cells (HOMTECs) are cultured in vitro. After exposure to bioincompatibility factors of PD solution, inflammation cytokines and uremic serum, expression of pericyte/ endothelial cell cross-talk related molecules, tight junction proteins as well as permeability of HOMTECs are determined; 3. Uremic PD animal model is constructed. Data are collected on changes in peritoneal vascular caliber, pericyte number, coverage rate, phenotype, and expression of PDGF-B/PDGFR-β and Angpt/Tie2. Vascular leakness is measured and peritoneal equilibrium test is used to evaluate peritoneal permeability and function. Effects of interfering the pericyte/ endothelial cell cross-talk will be investigated by intraperitoneal administering DNA aptamer AX102, which is a selective PDGF-B-blocking oligonucleotide, and the angiopoietin 1 mimic COMP-Angpt1. This study explores the mechanism of high peritoneal permeability during long-term PD through pericyte/ endothelial cell cross-talk pathway, and might provide a novel target for prevention and treatment of peritoneal membrane failure.